ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.1190A>G (p.His397Arg) (rs876661021)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217559 SCV000279215 uncertain significance not provided 2015-10-28 criteria provided, single submitter clinical testing This variant is denoted PTEN c.1190A>G at the cDNA level, p.His397Arg (H397R) at the protein level, and results in the change of a Histidine to an Arginine (CAT>CGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PTEN His397Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Histidine and Arginine share similar properties, this is considered a conservative amino acid substitution. PTEN His397Arg occurs at a position that is conserved across species and is located in the C-terminal domain (Nguyen 2013). Based on currently available evidence, it is unclear whether PTEN His397Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000801836 SCV000941633 uncertain significance PTEN hamartoma tumor syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 397 of the PTEN protein (p.His397Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 234434). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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